ABSTRACT Gastroparesis (GP) is defined as delayed gastric emptying in the absence of a gross structural abnormality with the symptoms chronic nausea and vomiting, early satiety, postprandial fullness, and abdominal distention. Pain or discomfort is frequently associated. A factor associated with improvement was anti-depressant use and factors associated with no symptom reduction included use of pain modulators, moderate to severe abdominal pain, and moderate to severe depression. The common theme of poor prognosis are factors which may arise from pathology that exist beyond just enteric motor function despite the fact that gastroparesis is indeed initially defined as an enteric motor disorder. Although the causes of gastroparesis can be multi-factorial, when the disease becomes chronic and the severity of the symptoms result in a high impact on Quality of Life (QOL), complex pathologies may begin to evolve in the enteric and central nervous system beyond just motor abnormalities contributing to other sensory defects. The neurobiology of these other factors needs to be explored further so that these insights can be translated into meaningful increases in treatment success in the moderate to severe gastroparetic patients. To accomplish these goals, we propose to create an additional site with the New England Gastroparesis Collaborative to join the NIH GR. The multi-center network will help recruit to our proposal to explore the peripheral and central neurobiology of gastroparesis and as well as help to conduct a Cognitive Behavioral Therapy (CBT) intervention to target these challenging pathologies. We plan to explore the relationships with gastroparesis symptoms, clinical co- comorbidities such as pain, depression, anxiety and catastrophization, and other GI physiological testing such as gastric emptying scitigraphy (GES), Wireless Motility Capsule (WMC), Electrogastrography (EGG) and Liquid Meal Satiety Drink Tests (SDT). We will perform a placebo controlled CBT trial in GP to examine the non- pharmacological impact of this treatment option on gastroparesis symptoms and the other clinical co-comorbidities such as pain, depression, anxiety and catastrophization. A subset of the CBT trial patients will undergo careful phenotyping pre/post intervention with brain MRI, AFT, and other GI physiological testing: GES, WMC, EGG and SDT to determine the impact of CBT on these physiologies. Characterization of these relationships or lack thereof can help guide future development of more targeted effective approaches in gastroparesis.